Imaging Science in Dentistry 2019; 49: 71-7

https://doi.org/10.5624/isd.2019.49.1.71

Delayed diagnosis of a primary intraosseous squamous cell carcinoma: A case report

1,*
Ahmed Z. Abdelkarim , Ahmed M. Elzayat 2
, Ali Z. Syed 3
, Scott Lozanoff 1

1
Department of Anatomy, Biochemistry and Physiology, University of Hawai’i School of Medicine, Honolulu, HI, USA
2
Department of Oral and Maxillofacial Surgery, Insurance Hospital, Suez, Egypt
3
Oral and Maxillofacial Medicine and Diagnostics Science, CWRU School of Dental Medicine, Cleveland, OH, USA

ABSTRACT

Primary intraosseous squamous cell carcinoma is a rare malignant central jaw tumor derived from odontogenic epithelial
remnants. Predominantly, it affects mandible, although both jaw bones may be involved. This report describes a 60-year-
old man who was initially misdiagnosed with a periapical infection related to the right lower wisdom tooth. After
four months, the patient presented to a private dental clinic with a massive swelling at the right side of the mandible.
Panoramic radiographs and advanced imaging revealed a lesion with complete erosion of the right ramus, which
extended to the orbital floor. A biopsy from the mandibular angle revealed large pleomorphic atypical squamous cells,
which is the primary microscopic feature of a poorly differentiated squamous cell carcinoma. (Imaging Sci Dent 2019;
49: 71-1)

KEY WORDS: C
‌ arcinoma, Squamous Cell; Mandible; Delayed Diagnosis; Computed Tomography, X-Ray; Magnetic Resonance Imaging

Primary intraosseous squamous cell carcinoma (PIOSCC)
is an uncommon neoplasm, defined as a squamous cell
carcinoma (SCC) that develops within the jaw bones and
arises from remnants of odontogenic epithelium with no
initial connection to the oral mucosa.1 In 2005, the World
Health Organization (WHO) divided PIOSCC into 3 types:
solid-type carcinoma, carcinoma arising from a keratocystic
odontogenic tumor, and carcinoma arising from an odon-
togenic cyst.2 The definitive diagnosis of PIOSCC is often
problematic, and the diagnostic criteria for PIOSCC still
remains elusive. Some studies have reported that one of the
histopathological definitions of PIOSCC is a SCC arising
within the jawbone that does not involve the oral mucosa.3,4
PIOSCC is estimated to account for 12% of all cases of
oral cancer.1 The majority of PIOSCCs arise from odonto-
genic cysts, including dentigerous cysts and keratocystic
odontogenic tumors, and only rarely do they originate from
residual periapical cysts.5 Commonly reported clinical fea-
tures of PIOSCC include jaw swelling, pain, and sensory
Received August 26, 2018; Revised October 18, 2018; Accepted November 18, 2018
*Correspondence to: Dr. Ahmed Z. Abdelkarim
Department of Anatomy, Biochemistry and Physiology, University of Hawai’i
School of Medicine, Honolulu, HI 96813, USA
Tel) 1-808-725-9954, E-mail) ahmedz@hawaii.edu
disturbances.4 Before the diagnosis of PIOSCC, the exis-
tence of a primary tumor in another site must be ruled out.4
Histological findings are often not pathognomonic for the
diagnosis of PIOSCC.5
The radiographic features of PIOSCC show considerable
variation both within and between each type.6 Solid-type
PIOSCC commonly displays an osteolytic appearance
with ill-defined irregular margins, whereas the other types
are often indistinguishable from benign jawbone lesions
with well-defined margins during the initial phase.2 Larger
PIOSCCs of all kinds have various destructive effects on
the jawbone.2
The purpose of this article is to present a case of PIO
SCC, along with a review of the clinical, radiological, and
microscopic characteristics of PIOSCC that led to a de-
layed diagnosis. This case adds to the very few instances of
definitive PIOSCC diagnosis described in the literature.
Case Report
In March 2018, a 60-year-old man presented to a private
dental clinic with a history of painful swelling in the right
angle of the mandible. The patient reported that in December
2017, he had visited another local dental clinic with a chief

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0)
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Imaging Science in Dentistry·pISSN 2233-7822 eISSN 2233-7830

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Delayed diagnosis of a primary intraosseous squamous cell carcinoma: A case report
A examination and panoramic radio-
complaint related to pain in the right posterior mandibular
region. His past medical history included controlled type 2
diabetes. The dentist requested a panoramic radiograph, and
the diagnosis was a periapical infection related to the right
third molar and badly decayed right second molar, and an
extraction was performed based on the patient’s history. Af-
ter extraction, the patient reported continuous pain with an
unhealed socket, and an antibiotic regime was initiated. As
a result of the unresolved pain, and without a prescription
from his physician, he packed the unhealed wound with di-
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Fig. 1. Panoramic radiograph shows
an ill-defined radiolucent lesion pos-
terior to the right third molar with
erosion of the inferior border of the
mandible.
Fig. 2. Clinical picture over extraoral
graph. A. Supine and lateral views
show a large swelling at the right
side of the face. B. Panoramic radio-
graph shows complete erosion of the
right ramus, condyle, and a portion
of the mandibular body.
clofenac sodium daily.
A panoramic radiograph was acquired from his first visit
(Fig. 1), and it revealed an ill-defined radiolucent lesion
posterior to the right third molar, as well as an abnormally
irregular inferior border of the mandible. The clinical ex-
amination record did not mention any observation of an in-
traoral soft tissue mass or ulceration at that time. An extra-
oral examination revealed a swelling with paresthesia in the
right mandibular angle (Fig. 2A). A panoramic radiograph
was requested and showed complete erosion of the right ra-

mus, with the lesion extending to the body of the mandible
(Fig. 2B). The radiographic signs were highly suggestive of
aggressive neoplastic changes, and advanced imaging was
therefore recommended. Multi-slice computed tomography
without contrast revealed a large soft-tissue mass lesion
occupying the right side of the parapharyngeal region, ex-
tending from the inferior orbital margin to the lower neck
region, resulting in a prominent right anterolateral contour
bulge (Fig. 3). The lesion had infiltrated the masseter mus-
cle. A complete absence of the right mandibular ramus and
temporomandibular joint (TMJ) was observed, as well as
erosion of the distal mandibular body. The right maxillary
sinus showed erosion of its posterolateral boundary, mild
mucosal thickening, and a large cyst with a calcific margin
and fluid content. The left TMJ was intact, and no osteoar-
thritic changes were noticed. These imaging features sug-
gested a large, osteolytic, neoplastic lesion.
Magnetic resonance imaging (MRI) was performed in the
head and neck region to reveal the soft-tissue extent of the
lesion mass (Fig. 4). A large irregular heterogenous soft tis-
sue mass involving the right hemi-mandible was observed,
including the condylar and coronoid processes and the man-
dibular ramus, and most of the mandibular body had been
replaced by a broad, ill-defined, soft-tissue mass lesion
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Ahmed Z. Abdelkarim et al
measuring 8.8 × 4.5 × 5 cm. The lesion was seen extending
superiorly into the mandibular fossa of the temporal bone,
inferiorly to the level of the C3 vertebra, and medially in-
volving the medial and lateral pterygoid muscles. Laterally,
the lesion had invaded the masseter muscle and extended
into the right subcutaneous facial fat planes, with an indis-
tinct line of cleavage from the parotid gland. Posteriorly,
it was seen to be intimately related to the right maxillary
artery. The mass displayed a low signal in T1 imaging, and
an intermediate signal in T2 imaging, with hyperintense
foci. In post-contrast T1 imaging, the lesion showed intense
post-contrast enhancement and was seen to have infiltrated
the adjacent muscles.
Another well-defined rounded lesion, measuring 2 ×
2.2 × 2.3 cm with a similar imaging pattern, was observed
inferior to the neoplasm. It was closely related to the right
submandibular gland, with a vague line of cleavage. In the
right maxillary sinus, a soft-tissue mass (predominantly
low-signal in T1 imaging and high-signal with a low-sig-
nal area in the center in T2 imaging) was seen, measuring
2 × 2.5 cm, along with an obliterated osteomeatal complex
and invasion of the inferomedial maxillary wall with sig-
nificant post-contrast enhancement (Fig. 4C). These MRI
features of the maxillary lesion indicated that the content
Fig. 3. Multi-slice computed tomog-
raphy. A 3-dimensional reconstruc-
tion image shows complete erosion
of the ramus. Axial, coronal, and
sagittal slices show extension of the
lesion (red arrows).
Delayed diagnosis of a primary intraosseous squamous cell carcinoma: A case report

Fig. 4. Magnetic resonance imaging examination. Series of axial T1 (A), T2 (B), and post-contrast axial T1 (C) images showing the extension
of the lesion (arrows) in the pterygoid region, maxillary sinus, and submandibular area (columns from left to right).

was an inflammatory process not consistent with the main
lesion. This excluded the possibility that the main lesion
extended to the sinus, and the lesion in that area was diag-
nosed as sinusitis. Multiple bilateral enhancing subman-
dibular and upper cervical enlarged lymph nodes were
noticed, with the most significant measuring 1.4 cm on the
right side. The differential diagnoses were odontogenic car-
cinoma, metastatic carcinoma, and sarcoma.
Two specimens were taken for histopathological ex-
amination (Fig. 5). The first specimen was obtained from

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 Ahmed Z. Abdelkarim et al

A B

C D

Fig. 5. Gross biopsy and histopathology examination. A. Two specimens from the angle of the mandible (3 pieces, left) and the maxillary si-
nus (multiple pieces, right). B. Section shows groups of large pleomorphic atypical squamous cells (arrows) with a high nucleoplasm ratio and
focal intracytoplasmic keratin formation (H&E stain, × 400). C. Numerous irregularly shaped solid epithelial islands of varying sizes in the
connective tissue (H&E stain, × 40). D. The basal cells are arranged in a plexiform pattern with palisading of the peripheral cells (H&E stain,
× 100) (red arrows).

the soft tissue mass around the angle of the mandible by
an extraoral approach. The second sample was obtained
from the maxillary sinus by enucleation of the cyst using
Caldwell-Luc antrostomy (Fig. 5A). For the first specimen,
the microscopic examination revealed fibro-fatty tissue
infiltrated by a tumor mass of large pleomorphic atypical
squamous cells with a high nucleoplasm ratio and focal in-
tracytoplasmic keratin formation (Fig. 5B). The intervening
stroma was heavily infiltrated by mixed inflammatory cells
with numerous mitotic figures. Histopathological examina-
tion of hematoxylin and eosin-stained slides showed plen-
tiful irregular-shaped solid epithelial islands of differing
sizes in the connective tissue (Fig. 5C). The basal cells vw-
ere arranged in a plexiform pattern with palisading of the
peripheral cells (Fig. 5D). Microscopic examination of the
maxillary sinus specimen revealed soft tissue infiltrated by
lymphocytes, plasma cells, and fragments of necrotic bony
spicules. Based on the microscopic findings, a final diag-
nosis of solid-type PIOSCC was made.
Discussion
In this case report, the authors present a very rare case of
PIOSCC. Diagnosis of PIOSCC may be difficult, as it must
be differentiated from carcinoma arising from the epithelial
lining of the maxillary sinus, from carcinoma originating
from the alveolar mucosa epithelium that has invaded the
bone, and from tumor metastasis to the jaw. Due to its rari-
ty, its incidence, prevalence, and etiology are still not fully
understood.7
PIOSCC is a rare malignant odontogenic tumor that
accounts for approximately 1%-2.5% of all odontogenic

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Delayed diagnosis of a primary intraosseous squamous cell carcinoma: A case report
tumors.8 PIOSCC displays a predilection for males (2 : 1
male-to-female ratio).2 Although it can occur at any age, it
most commonly occurs in the fifth decade of life.1 PIOSCC
is more often found in the mandibular body and posterior
mandible than in the maxilla.1 In our case, a 60-year-old
male patient was affected, and the lesion in the present case
involved the masticator space and the infra-temporal region
up to the level of the cranial base.
These findings are similar to the data published by Huang
et al.,9 who studied a total of 39 PIOSCCs (solid type) at
Peking University School and Hospital of Stomatology
(Beijing, China) from 1985 to 2006. Their findings are in
concordance with those of Thomas et al.10 The etiology of
PIOSCC is unclear, but the most common factor may be a
reactive inflammatory stimulus with or without a predispos-
ing genetic cofactor.10
Clinically, PIOSCC is associated with various symptoms
depending on its location, size, and type. These symptoms
include pain, swelling, sensory disturbances, and routine
dental disorders.11 The 60-year-old male patient described
herein experienced a tingling sensation in the lower left gin-
giva of his molar region with paresthesia of the lower lip.
The radiological and clinical characteristics of PIOSCCs
are similar to those of odontogenic tumors. In some in-
stances, early-stage PIOSCC may mimic routine dental
disorders, such as periapical and periodontal disease, which
may lead to misdiagnosis or delayed diagnosis.12 In our
case, the patient’s first dentist misdiagnosed the lesion, in
its early stage, as an inflammatory odontogenic condition.
Radiographically, in most cases, osteolytic bone changes
are characterized by poorly defined, diffuse, and irregular
margins.13 As presented in Figure 1, the lesion showed sim-
ilar features, with erosion at the inferior mandibular border.
MRI has advantages over other imaging techniques for
the anatomical assessment of head and neck cancers, espe-
cially with regard to mapping the primary tumor extent.14
For this patient, the primary lesion involved the masticator
space with extension to the infratemporal fossa and adja-
cent muscles. MRI ruled out the extension of the lesion to
the maxillary sinus.
The definitive diagnosis of PIOSCC is often challenging,
since malignant tumors that have metastasized to the jaw
from distant sites, tumors originating from the maxillary
sinus, and alveolar carcinomas that have invaded the bone
from the surface must be ruled out.15 In the present case,
the differential diagnoses were odontogenic carcinoma,
metastatic carcinoma, or sarcoma. This differential diag-
nosis was formulated because the radiographic lesion was
destructive, with ill-defined and ragged borders. The possi-
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bility of a metastatic tumor was excluded since the patient
had no history of a primary tumor elsewhere in the body.
Osteosarcoma and chondrosarcoma were considered. Chon-
drosarcomas are rarely found in the jaws, and generally
occur in the anterior alveolar process of the maxilla, the al-
veolar ridge of the premolar-molar region, and the angle of
the mandible. However, they are painless and slow-growing
in their early stages. Osteosarcomas are rarely seen in the
jaw bones, which account for only 7% of all cases, but are
more frequently seen in long bones. Moreover, osteosar-
comas generally show a moth-eaten appearance due their
rapid growth pattern in the initial osteolytic stage. The age
of occurrence is mainly during the third decade of life. In
the case described herein, the radiographic findings did not
show a sunray appearance and Codman’s triangle, which
are commonly seen in cases of osteosarcoma.7
PIOSCC, which develops from remnants of the odonto-
genic epithelium, is defined as an SCC arising within the
jawbones. In 1972, the WHO suggested the term primary
intraosseous odontogenic carcinoma (PIOC).11 Subsequently,
the WHO classification was modified by adding ameloblastic
carcinoma.12 The classification was further revised in 1984,16
and intraosseous mucoepidermoid carcinoma was added to
the classification of PIOC in 1989.17 In 2005, the WHO es-
tablished the term PIOSCC and categorized it into 3 types:
solid-type carcinoma, carcinoma arising from a keratocystic
odontogenic tumor, and carcinoma arising from an odonto-
genic cyst.2 The detailed subcategories of PIOSCC reflect
3 characteristic etiological processes. PIOSCC can arise as
a solid tumor invades the marrow space and induces osse-
ous resorption, as an SCC originating from the lining of an
odontogenic cyst, or as an SCC associated with other benign
epithelial odontogenic tumors.2,3 In the present case, a his-
topathological examination revealed that a tumor mass was
growing in the bone, and no finding was indicative of direct
invasion of the SCC from the covering squamous epithelium.
This conclusion was also supported by the clinical history of
the patient’s first visit. The tumor cells displayed the char-
acteristic features of SCC. No signs were found of another
odontogenic cyst or tumor, or of any other primary SCC.
In conclusion, the present case highlights the importance
of a thorough interpretation of radiographs, as failure to
read radiographs thoroughly could potentially delay the di-
agnosis or lead to a misdiagnosis, as happened in this case.
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